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COMPARATIVE EVALUATION OF PREDNISOLONE
5MG TABLETS MARKETED IN BANGLADESH
A PROJECT SUBMITTED TO THE DEPARTMENT OF PHARMACY,
BRAC UNIVERSITY
IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE DEGREE OF
BACHELOR OF PHARMACY
SUBMITTED BY:
NABILA MORSHED
ID: 11146002
SESSION: SPRING 2011
SUBMISSION ON: MARCH 2015
DEPARTMENT OF PHARMACY
BRAC UNIVERSITY
I
Acknowledgement
I would like to express my thanks and gratitude to the Department of Pharmacy, BRAC
University for providing me the laboratory facilities for the completion of the project. I am also
thankful to my supervisor, Ms. Shahana Sharmin for her dedicated supervision and obliged to all
those who have given me their valuable time and energy from their hectic work schedule to
express their full experience about the instrumental terms, conditions and working procedures.
Special thanks to the GlaxoSmithKline (Bd) Ltd. Pharmaceuticals for proving us the working
standard.
I want to specially acknowledge for the immense support, helpful and creative contributions of
the following people:

Professor Mohammad Shawkat Ali, Chairperson, Department of Pharmacy, BRAC
University.

Ms. Shahana Sharmin, Senior Lecturer, Department of Pharmacy, BRAC University.
II
Abstract
The aim of the present study is to determine the quality and to correlate with other different
brands of pharmaceutical products marketed in Bangladesh for the healthcare of patients
suffering from different respiratory inflammation like asthma, and auto-immune disorders. The
experiment is done to evaluate and compare the physicochemical equivalence of different brands
of Prednisolone 5mg tablet. These tablets were tested through statistical methods in accordance
with the BP and USP like weight variation, thickness, hardness, friability, disintegration, in-vitro
dissolution and HPLC assay. The in vitro dissolution studies of Prednisolone 5 mg tablets were
carried out in pH 7 distilled water for 30 minutes using USP-II method whose absorbance were
taken at 246 nm using UV spectrophotometry. Six samples showed poor in-vitrodissolution
whichwere non-equivalent to the USP monograph specification giving Prednisolone content less
than 75%. The percentage content of active ingredient of different brands were tested using
HPLC assay. Samples showed values within the specifications (90-110%) except some of the
companies. Two samples did not undergo disintegration at all when given in the disintegration
tester. However, no major problem was found in others physical parameters like tablet weight
variation, thickness, hardness and friability. Finally from the experiment we can conclude that
50% of the companies in the urban area are substandard, whereas 50% companies provide
standard drugs.
III
Contents
Page Number
Chapter 1
1.1 Introduction……………..……………………………………………………………………..2
1.2 Conventional dosage forms……………..……………………………………………………..2
1.3 Advantages of conventional dosage forms……….. ……………………………………….....3
1.4 Disadvantages of conventional dosage forms……………….………………………………...3
1.5 Diseases which are treated with Prednisolone………………………..……………………..3-4
1.6 Drug profile……………………………………………………………………..………….….5
1.7 Mechanism of action…………………………………………………………………………..6
1.8 Pharmacodynamic properties……………………………………………………………….....7
1.9 Pharmacokinetic properties……………………………………………………………………7
1.10 Dosage and Administration………………………………………………………………..7-9
1.11 Adverse effects……………………………………………………………..………….....9-10
1.12 Side effects………………………………………………………………………………….10
1.13 Contraindications……………………………………………………………...……………11
1.14 Use during pregnancy…………………………………………………………….……...…11
1.15 Drug interactions………………………………………………………………………..12-13
1.16 Available dosage forms of Prednisolone in Bangladesh………………………..………14-15
Chapter 2
Page Number
2.1 Materials………………………………………………………………………………….17-23
2.2 Assay of Prednisolone by High Performance Liquid Chromatography (HPLC) ……….24-25
2.3 In-vitro dissolution study…………………………………………………………………26-28
2.4 Physical parameters of Prednisolone……………………………………………………..29-30
2.5 Collection of sample…………………………………………………………………………30
IV
Chapter 3 Results and Discussion
Page Number
3.1 HPLC assay values of Prednisolone tablets of five different companies……..….………32-41
3.2 In-vitro dissolution study results………………………………….………………...……42-43
3.3 Physical analysis……………………………………………………………………….…….44
3.4 Weight Variation…………………………………………………………………………45-46
3.5 Thickness………………………………………………………………………..………..47-48
3.6 Hardness……………………………………………………………………………….…49-50
3.7 Friability…………………………………………………………………………..……...51-52
3.8 Disintegration time……………………………………………………………………….53-54
4. Conclusion…………………………………………………………………………..……..55-56
References………………………………………………………………………………………..57
V
List of tables:
Page number
Table 1.1: Table showing the available dosage forms of Prednisolone in Bangladesh………….14
Table2.1: List of instruments and equipment used in the analysis………………………………17
Table2.2: List of apparatus and glass wares used in the experiment……………………...……..18
Table 2.3: List of tablets from different samples and their batch number and expiry date …......19
Table 2.4: Standard curve of Prednisolone………………………………………………………27
Table 3.1: Percentage of Prednisolone content of tablets of different samples…………..……...32
Table 3.2: Table of in-vitro dissolution of Prednisolone tablets of different samples………......42
Table 3.3: Table showing shapes of different samples…………………………………………..44
Table 3.4: Table showing weight variation of ten tablets of each samples……………………...45
Table 3.5 Table showing thickness variability of ten tablets of different samples…………...…47
Table 3.6: Table showing hardness variability of ten tablets of different samples……..….……49
Table 3.7: Friability test of different samples and their total weight before and
after the test...…………………………………………………………………………………….51
Table 3.8: Table showing the disintegration time of different samples………………………….53
VI
List of figures
Page number
Figure 1.1: Picture of Cortan® 5mg & 20mg Prednisolone tablets manufactured and marketed by
Incepta Pharmaceuticals Ltd. ……………………………………………………………………15
Figure 1.2: Picture of Inflagic® 5mg tablets manufactured and marketed by Square
Pharmaceuticals Ltd. …………………………………………………………………………….15
Figure 2.1: Picture showing slide caliper………………………………………………………...20
Figure 2.2: Picture showing an electronic balance………………………………………………20
Figure 2.3: Tablet friability tester………………………………………………………………..20
Figure 2.4: Picture showing disintegration tester………………………………………………..20
Figure 2.5: Picture showing UV-Visible spectrophotometer…………………………………….21
Figure 2.6: Picture showing dissolution tester…………………………………………………...21
Figure 2.7: Picture showing the paddle of dissolution tester…………………………………….22
Figure 2.8: Picture showing the HPLC machine………………………………………………...23
Figure 2.3.1: Standard curve of Prednisolone…………………………………………………...27
Figure 3.1: Bar chart showing percentage of Prednisolone content of different samples……….33
Figure 3.1.1: HPLC report of Prednisolone standard 1………………………………………….34
Figure3.1.2: HPLC report of Prednisolone standard 2…………………………………….…….35
Figure 3.1.3: HPLC report of Prednisolone sample 1……………………………………………36
Figure 3.1.4: HPLC report of Prednisolone sample 2……………………………………………37
Figure 3.1.5: HPLC report of Prednisolone sample 3……………………………………………38
Figure 3.1.6: HPLC report of Prednisolone sample 4…………………………………...……….39
Figure 3.1.7: HPLC report of Prednisolone sample 5……………………………………………40
Figure 3.1.8: HPLC report of Prednisolone sample 6....................................................................41
Figure 3.2: Bar chart of in-vitro dissolution of Prednisolone tablets of different samples…..…..43
Figure 3.3: Bar chart showing weight variation of ten tablets of different samples……….…….46
Figure 3.4: Bar chart showing thickness variability of ten tablets of different
samples…………………………………………………………………………………………..48
Figure 3.5 Hardness variability of ten tablets of different samples……………………………...50
Figure 3.6: Bar chart of friability test of different samples and their total weight before and after
the test…………………………………………………………………………………..…….….52
VII
Figure 3.7: Bar chart showing the different disintegration time of different samples…………..54
VIII
Chapter 1:
Introduction
1
1.1Introduction
Medicines need to be safe, effective and of good quality in order to produce the desired effect.
Ensuring these properties requires the creation of competent national drug regulatory authorities
with the necessary human and other resources to control the manufacture, importation,
distribution and sale of medicines. The necessity of any drug delivery system is to provide a
therapeutic amount of drug to the proper site in the body and then maintain the optimum plasma
concentration for a definite period of time. The quality of a drug is an important factor which
ensures the health and wellness of a patient. Substandard quality of drugs increases the mortality
and morbidity in a country. The objective of this project is to evaluate the quality of drug
available in Bangladesh market which is being used for patients suffering from respiratory
disorders and various auto-immune disorders.
1.2 Conventional Dosage forms:
Tablets are solid dosage forms usually obtained by single or multiple compressions of powders
or granules. In certain cases tablets may be obtained by molding or extrusion techniques. They
are uncoated or coated.Tabletscontain one or more active ingredients. They may contain
excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances
capable of modifying the behavior of the dosage forms and the active ingredient in the
gastrointestinal tract, coloring matter authorized by the appropriate national or regional authority
and flavoring substances. When such excipients are used it is necessary to ensure that they do not
adversely affect the stability, dissolution rate, bioavailability, safety or efficacy of the active
ingredient; there must be no incompatibility between any of the components of the dosage
form.Tablets are single-dose preparations intended for oral administration. Some are intended to
be swallowed whole, some after being chewed and some after being crushed, some are intended
to be dissolved or dispersed in water before being taken and some are intended to be retained in
the mouth where the active ingredient is liberated. 1
2
1.3 Advantages of conventional dosage forms:
a. They are unit dose form, and they offer the greatest capabilities of all dosage forms for the
greatest dose precision and the latest content variability.
b. their cost is lowest of all dosage forms
c. They are the lightest and most compact of all oral dosage forms
d. They are in general the easiest and cheapest to package and ship of all oral dosage forms
e. Product identification is potentially the simplest and cheapest, requiring no additional
processing steps when employing an embossed or monogrammed punch face.
f. They may provide the greatest ease of swallowing with the least tendency for ‘hang-up’ above
stomach, especially when coated provided that tablet disintegration is not excessively rapid.
g. they lend themselves to certain special release profile products such as enteric or delayedrelease products.
h. They are better suited to large scale production than other unit oral forms
i. They have the best combined properties of chemical, mechanical and microbiologic stability of
all oral forms.
1.4 Disadvantages of conventional oral dosage forms:
a. Some drugs resist compression into dense compacts, owing to their amorphous nature or
flocculent, low-density character.
b. Drugs with poor wetting, slow dissolution properties, intermediate to large dosages, optimum
absorption high in the gastrointestinal tract, or any combination of these features may be difficult
or impossible to formulate and manufacture as a tablet that will still provide adequate or full drug
bioavailability.
c. Bitter tasting drugs, drugs with an objectionable odor, or drugs that are sensitive to oxygen or
atmospheric moisture may require encapsulation or entrapment prior to compression or the
tablets may require coating.2
1.5 Diseases which are treated with prednisolone:
Respiratory disorders are an increasing day by day and affecting majority of people due to
increasing air pollution. Glucocorticoids are commonly used to treat a wide range of respiratory
inflammatory diseases like asthma. They are thought to decrease the chronic inflammation in the
3
bronchiole tree, thereby improving obstructed airflow. The main API (active pharmaceutical
ingredient) of this project is prednisolone. Prednisolone is a corticosteroid drug with
predominant glucocorticoid and low mineralocorticoid activity, making it useful for the
treatment of a wide range of inflammatory and auto-immune conditions such as asthma.
Prednisolone can also be used as an immunosuppressive drug for organ transplants and in cases
of adrenal insufficiency (Addison's disease).3 Prednisolone is a man-made form of a natural
substance (corticosteroid hormone) made by the adrenal gland. It is used to treat conditions such
as arthritis, blood problems, immune system disorders, skin and eye conditions, breathing
problems, cancer, and severe allergies. It decreases immune system's response to various
diseases to reduce symptoms such as pain, swelling and allergic-type reactions.
Corticosteroids inhibit the inflammatory response to a variety of inciting agents and, it is
presumed, delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation,
leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and
scar formation with inflammation.4Corticosteroids are considered to be one of the most effective
medicines for asthma by suppressing airway inflammation.12
The WHO has been tracking and documenting the incidences of substandard drugs. The records
show that problems of substandard and counterfeit drugs are on increase as 50% of all reported
cases occurred in the period 1993 to 1997. Most of these incidences (70%) were reported in
developing countries. The report identifies the causes of the poor quality of drugs: in about 50%
of all the cases the formulations did not contain any drug, 20% contained the wrong active
ingredient and 10% the wrong amount of the active ingredient. Only in 5% of the reported
incidences did the drugs contain the right active ingredient in the correct amounts, but were
judged substandard by failing other quality tests.5
9 percent of pharmaceutical sales in Bangladesh have been traced to counterfeit or low-quality
drugs, openly sold in pharmacies.6
This project focuses on the evaluation of the prednisolone dosage form and its basic parameters
which evaluated the drug quality and shows whether they meet the USP requirements as claimed
by the manufacturing companies.
4
1.6 Drug Profile:
Active Pharmaceutical Ingredient: Prednisolone
Therapeutic Class: Endocrine-metabolic agent, immune suppressant
Therapeutic Indications:
i. Skin: Pemphigus vulgaris, allergic dermatitis, eczema, exfolliative dermatitis, dermatitis herpetic
formas, dermatitis medicamentosa, erythema multiforme, disseminated lupus erythematosus,
dermatomyositis, polyarteritisnodosa.
ii. Respiratory: Severe bronchial asthma and status asthmaticus, emphysema,pulmonary fibrosis.
iii. Adrenal: Adrenal hyperplasia (adrenogenital syndrome).
iv. Haematological: Idiopathic thrombocytopenic purpura, acquired haemolytic anaemia,
acuteleukaemia.
v. Other: Nephrotic syndrome, iridochoroiditis ulcerative colitis, rheumatoid arthritis, ankylosing
spondylitis, rheumatic fever, gout, periarthritis of the shoulder.
Description: Prednisolone is a synthetic glucocorticoid, a derivative of cortisol which is used to
treat a variety of inflammatory and auto-immune conditions. It is the active metabolite of drug
prednisone and it is used in patients with hepatic failure as they are unable to metabolize
prednisone to prednisolone. 7
Systemic (IUPAC) name: (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3one
Molecular formula: C21H28O5
Molecular Mass: 360.44402g/mol
5
Structural formula:
Appearance: White to white crystalline powder
Solubility: in water, 2.23X10+2mg/L at 25° C
Melting point:235°C
1.7 Mechanism of action:
Prednisolone can inhibit leukocyte infiltration at the site of inflammation, interfere with
mediators of inflammatory response, and suppress humoral immune responses. The ant
antinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory
proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as
prostaglandins and leukotrienes. Prednisolone reduces inflammatory reaction by limiting the
capillary dilatation and permeability of the vascular structures. These compounds restrict the
accumulation of polymorphonuclear
honuclear leukocytes and macrophages and reduce the release of
vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of
arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins.
Prednisolone iss a glucocorticoid receptor agonist. On binding, the corticoreceptor
corticoreceptor-ligand
complex translocate itself into the cell nucleus, where it binds to many glucocorticoid response
elements (GRE) in the promoter region of the target genes. The DNA bound receptor tthen
interacts with basic transcription factors, causing an increase or decrease in expression of
specific target genes, including suppression of IL2 (interleukin 2) expression.8
6
1.8 Pharmacodynamic properties:
Prednisolone acts through replacing adrenal insufficiency as in Addison’s disease, or after
adrenalectomy. Prednisolone has anti-inflammatory and immuno-suppressant glucocorticoid
properties.
1.9 Pharmacokinetic properties:
Prednisolone is absorbed from the gastro-intestinal tract and peak plasma concentrations are
obtained 1 to 2 hours after administration. The drug has a plasma half-life of 2-3 hours and is
extensively bound to plasma protein. Prednisolone is excreted in the urine as free and conjugated
metabolites, together with an appreciable amount of unchanged Prednisolone. Prednisolone
crosses the placenta and small amounts are excreted in breast milk. The biological half-life of
Prednisolone lasts for several hours.9
1.10 Dosage and Administration:
Route of administration: oral
The lowest dose to produce an acceptable result should be given; when it is possible to reduce
the dose this must be by stages. In prolonged treatment, the dose may be increased temporarily
during periods of stress or exacerbation of illness.
Adults:
Short term treatment: 20 to 30mg daily for the first few days, reducing by 2.5 to 5mg every 2 to 5
days according to the response.
Rheumatoid arthritis: Initially 7.5 to 10mg daily reduced to the lowest effective dose for
maintenance.
Most other conditions: 10 to 100mg daily for 1 to 3 weeks, then reducing to the lowest effective
dose.
Elderly:
There is no evidence that the dosage should differ; the dose should be the minimum necessary to
achieve the desired therapeutic effect.
7
Children:
At 12 years, 75% of the adult dose; at 7 years, 50% of the adult dose; at 1 year 25% of the adult
dose dependent on clinical factors. Initial dose 0.75 to 1.0mg/kg of bodyweight daily, in divided
doses.10
Usual Adult Dose for Multiple Sclerosis:
Tablets and syrup for acute exacerbations: 200 mg daily for one week followed by 80 mg every
other day for 1 month.
Usual Adult Dose for Bronchopulmonary Dysplasia:
Tablets and syrup for acute exacerbations: 200 mg daily for one week followed by 80 mg every
other day for 1 month.
Usual Adult Dose for Anti-inflammatory:
Sodium phosphate:
Oral: 5 to 60 mg per day in divided doses 1 to 4 times/day.
Intravenous or Intramuscular: 4 to 60 mg/day
For intraarticular, intralesional or soft tissue administration:
Large joints: 10 to 20 mg
Small joints: 4 to 5 mg
Bursae: 10 to 15 mg
Tendon sheaths: 2 to 5 mg
Soft tissue infiltration: 10 to 30 mg
Ganglia: 5 to 10 mg
Injectable suspension (tebutate) for intraarticular, intralesional or soft tissue administration:
Large joints: 20 to 30 mg (doses > 40 mg not recommended)
Small joints: 8 to 10 mg
Bursae: 20 to 30 mg
Tendon sheaths: 4 to 10 mg
Ganglia: 10 to 20 mg
Injectable suspension (acetate) for intraarticular, intralesional or soft tissue administration: 4 to
100 mg
Bursae: 10 to 15 mg
8
Tendon sheaths: 2 to 5 mg
Soft tissue infiltration: 10 to 30 mg
Usual Pediatric Dose for Immunosuppression:
Oral: 0.1 to 2 mg/kg/day in divided doses 1 to 4 times a day.
Intravenous: 0.1 to 2 mg/kg/day in divided doses 1 to 4 times a day.
Usual Pediatric Dose for Asthma -- Acute:
Oral: 1 to 2 mg/kg/day in divided doses 1 to 2 times a day for 3 to 5 days.
Intravenous: 2 to 4 mg/kg/day divided 3 or 4 times a day.
Usual Pediatric Dose for Nephrotic Syndrome:
First 3 episodes: Initial dose: 2 mg/kg/day (maximum dose 80 mg/day) until urine is free of
protein for 3 consecutive days (maximum: 28 days); followed by 1 to 1.5 mg/kg/dose every other
day for 4 weeks.
Frequent relapses or long-term maintenance dose: 0.5 to 1 mg/kg/dose given every other day for
3 to 6 months.
Usual Pediatric Dose for Bronchopulmonary Dysplasia:
2 mg/kg/day orally divided twice daily for 5 days, followed by 1 mg/kg/day once daily for 3
days, followed by 1 mg/kg/dose every other day for 3 doses.14
1.11 Adverse Effects:
Body as a whole: leucocytosis, hypersensitivity including anaphylaxis, thromboembolism,
fatigue, malaise
Cardiovascular: congestive heart failure in susceptible patients, hypertension
Gastro-intestinal: dyspepsia, nausea, peptic ulceration with perforation and haemorrhage,
abdominal distension, abdominal pain, increased appetite which may result in weight gain,
diarrhoea, oesophageal ulceration, oesophageal candidiasis, acute pancreatitis
Musculoskeletal: proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular
osteonecrosis, tendon rupture, myalgia
Metabolic/Nutritional: sodium and water retention, hypokalaemic alkalosis, potassium loss,
negative nitrogen and calcium balance
Skin: impaired healing, hirsutism, skin atrophy, bruising, striae, telangiectasia, acne, increased
sweating, may suppress reactions to skin tests, pruritis, rash, urticarial
9
Endocrine: suppression of the hypothalamo-pituitary adrenal axis particularly in times of stress
as in trauma surgery or illness, growth suppression in infancy, childhood and adolescence,
menstrual irregularity and amenorrhoea. Cushingoidfacies, weight gain, impaired carbohydrate
tolerance with increased requirement for anti-diabetic therapy, manifestation of latent diabetes
mellitus, increased appetite.
Nervous system: euphoria, psychological dependence, depression, insomnia, dizziness,
headache, vertigo, raised intracranial pressure with papilloedemain children, usually after
treatment withdrawal. Aggravation of schizophrenia, Aggravation of epilepsy suicidal ideation,
mania, delusions, hallucinations, irritability anxiety, insomnia and cognitive dysfunction. In
adults the frequency of severe psychiatric reactions has been estimated to be 5-6%.
Eye disorders: increased intra-ocular pressure, glaucoma, papilloedema, posteriorsubcapsular
cataracts, exophthalmos, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal
disease
Anti-inflammatory and Immunosuppressive effects: increased susceptibility to and severity of
infections with suppression of clinical symptoms and signs. Opportunistic infections, recurrence
of dormant tuberculosis.
Withdrawal symptoms : Too rapid a reduction of prednisone following prolonged treatment
can lead to acute adrenal insufficiency, hypotension and death. A steroid withdrawal syndrome
seemingly unrelated to adrenocortical insufficiency may also occur and include symptoms such
as anorexia, nausea, vomiting, lethargy, headache, fever, weight loss, and/or hypotension.
1.12 Side Effects:
Some common side effects of Prednisolone are mentioned below:
fluid retention, weight gain, high blood pressure, potassium loss, headache, muscle weakness,
puffiness of and hair growth on the face, thinning and easy bruising of the skin, glaucoma,
cataracts, peptic ulceration, worsening of diabetes, irregular menses, growth retardation in
children, convulsions, and psychic disturbances.
10
1.13 Contraindications
Prednisolone is contraindicated in patients with: peptic ulcer,
osteoporosis, psychosesor severe psychoneuroses.
Prednisolone is usually contraindicated in the presence of acute infection
Administration of live virus vaccines
1.14 Use during Pregnancy
The ability of corticosteroids to cross the placenta varies between individual drugs, however,
88% of Prednisolone is inactivated as it crosses the placenta. Administration of corticosteroids
to pregnant animals can cause abnormalities of foetal development including cleft palate, intrauterine growth retardation and effects on brain growth and development. There is no evidence
that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft
palate/ lip in man.
However, when administered for prolonged periods or repeatedly during pregnancy,
corticosteroids may increase the risk of intra-uterine growth retardation.
Hypoadrenalism may, in theory occur in the neonate following prenatal exposure to
corticosteroids but usually resolves spontaneously following birth and is rarely clinically
important. As with all drugs, corticosteroids should only be prescribed when the benefits to the
mother and child outweigh the risks. When corticosteroids are essential however, patients with
normal pregnancies may be treated as though they were in the non-gravid state.10
Lactation
Corticosteroids are excreted in small amounts in breast milk. However doses of up to 40mg daily
of prednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking
higher doses than this may have a degree of adrenal suppression but the benefits of breastfeeding are likely to outweigh any theoretical risk.10
11
1.15 Drug Interactions:
Hepatic microsomal enzyme inducers: Medicines that induce hepatic enzyme cytochrome P450 isozyme 3A4 such as Phenobarbital, phenytoin, rifampicin, rifabutin, carbamazepine,
primidoneandamino-gluethimide may reduce the therapeutic efficacy of corticosteroids by
increasingthe rate of metabolism.
Hepatic microsomal enzyme inhibitors: Medicines that inhibit hepatic enzyme cytochrome P450 isozyme 3A4 such asketoconazole, ciclosporin or ritonavir may decrease glucocortiocoid
clearance. A reduction in prednisone dose may be needed to reduce the risk of adverse effects.
Antidiabetic Agents: Prednisolone may increase blood glucose levels. Patients may need dosage
adjustment of any concurrent anti-diabetic therapy.
Non-steroidal anti-inflammatory drugs (NSAIDs): Concomitant administration may increase
the risk of gastro-intestinal tract ulceration. Aspirin should be used cautiously in conjunction
with prednisone in patients with hypo-thrombinaemia. The renal clearance of salicylates is
increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. Patients
should be observed closely for adverse effects of either medicine.
Anticoagulants: Response to anticoagulants may be reduced or less often enhanced by
corticosteroids.
Antifungals: The risk of hypokalaemia may be increased with amphoteracin.
Cardiac glycosides: There is a risk of toxicity if hypokalaemia occurs due to prednisone
treatment.
Cytotoxic agents: There is an increased risk of haematological toxicity when prednisone is
given with methotrexate.
Mifepristone: The effect of corticosteroids may be reduced for 3-4 days after mifepristone.
Vaccines: Live vaccines should not be given to individuals with impaired immune
responsiveness. The antibody response to other vaccines may be diminished.
Oestrogens: Oestrogens may potentiate the effects of glucocorticoids. The dose of prednisone
may need to be adjusted if oestrogen therapy is commenced or stopped.
Somatropin: The growth promoting effect may be inhibited.
Sympathomimetics: There is an increased risk of hypokalaemia if high doses of corticosteroids
are given with high doses of salbutamol, salmeterol, terbutaline or formoteral.
12
Diuretics: Excessive potassium loss may be experienced if glucocorticoids and potassium
depleting diuretics (such as fursemide and thiazides) or carbonic anhydrase inhibitors (such as
acetazolamide) are given together.
Antacids: Concurrent use of antacids with prednisone may decrease absorption of these
glucocorticoids efficacy may be decreased sufficiently to require dosage adjustments in patients
receiving small doses of prednisone.
13
1.16 Available dosage forms of prednisolone in Bangladesh:
Brand Name
Dosage
Cortan
Prednisolone
Dosage Form
5mg, Tablet
10mg & 20mg
Deltacort
Manufacturer
Incepta Pharmaceuticals
Ltd.
Prednisolone 5mg
Film Coated Tablet
Desh
Pahrmaceuticals
Ltd.
Deltapred
Prednisolone 5mg
Film Coated Tablet
Ziska
Pharmaceuticals
Ltd.
Deltasone
Prednisolone
5mg, Tablet
Renata Ltd.
10mg & 20mg
G-prednisolone
Prednisolone 5mg
Film Coated Tablet
Gonoshasthya
Pharmaceuticals Ltd.
Precodil
Prednisolone
5mg
& Tablet
OpsoninPharma Limited
Tablet
Glaxo Smith kline(BD)
20mg
Prednelan
Prednisolone 20mg
Ltd
Prednicortil
Prednisolone 5mg
Tablet
GacoPharmceuticals
Ltd.
Prednisolone
Prednisolone 5mg
Tablet
Glaxo Smith kline(BD)
Ltd
Prexan
Prednisolone 5mg
Film Coated Tablet
Chemist
Laboratories
Ltd.
Redisone
Prednisolone 5mg
Film Coated Tablet
Rephco
Laboratories
Ltd.
Zenilon
Prednisolone 5mg
Film Coated Tablet
Zenith Pharmaceuticals
Ltd.
Table 1.1: Table showing the available dosage forms of prednisolone in Bangladesh
14
Figure 1.1: Picture of Cortan® 5mg& 20mg prednisolone tablets manufactured and marketed by
Incepta Pharmaceuticals Ltd.
Figure 1.2: Picture of Inflagic® 5mg tablets manufactured and marketed by Square
Pharmaceuticals Ltd.
15
Chapter 2:
Material and
Methods
16
2.1 Materials:
Serial
number
Instrument
Model/Manufacturer
Country of
origin
1.
Slide caliper (0-150X0.05mm)
2.
Electronic balance
Shimadzu
Japan
3.
Friabilator (USP)
Electrolab, EF-2
India
4.
Disintegration Tester (USP)
Electrolab, ED-2L
India
5.
Dissolution Tester
6.
UV-Visible Spectrophotometer
7.
High Performance Liquid
Chromatography (HPLC)
China
Logan Instruments Corp.,
UDT-804
USA
Hitachi
Japan
Shimadzu
Japan
8.
Sonicator
Shimadzu
Bangladesh
9.
pH meter
Shimadzu
Bangladesh
10.
Lab stirrer
Shimadzu
Bangladesh
11.
Water suction filtration
Shimadzu
Bangladesh
Table2.1: List of instruments and Equipment used in the analysis
17
Serial
Name
Specification
1.
Volumetric flask
10ml, 20ml, 50ml, 1000ml
2.
Pipette(graduated & volumetric)
1ml, 2ml, 4ml, 5ml, 10ml
3.
Beakers
4.
Funnel
Small, medium
5.
Measuring cylinder
500ml, 1000ml
6.
Pipette filler
Bangladesh
7.
Filter paper
Whitman
8.
Injection syringe with 0.45µ disk filter
Bangladesh
9.
Mortar & Pestle
Small, medium
Number
10ml, 25ml, 50ml, 100ml,
500ml, 1000ml
Table2.2: List of apparatus and glass wares used in the experiment
18
Sample Number
Batch No.
Expiry date
Sample 1
602-28-50
APR 16
Sample 2
602-28-50
MAY 16
Sample 3
13059 E0816
AUG
Sample 4
13059 E0816
AUG 16
Sample 5
B166
AUG 16
Sample 6
B167
AUG 16
Sample 7
336E0916
SEP 16
Sample 8
346E0916
SEP 16
Sample 9
408002
JULY 16
Sample 10
408004
SEP 16
Sample 11
B06E02 2017
FEB 17
Sample 12
B10E02 2017
FEB 17
Table 2.3: List of tablets from different samples and their batch number and expiry date
19
Pictures & Images of the Instruments:
Figure 2.1: Picture showing slide caliper
Figure 2.2: Picture showing an electronic balance
Figure 2.3: Tablet friability tester
Figure 2.4: Picture showing disintegration tester
20
Figure 2.5: Picture showing UV-Visible spectrophotometer
Figure 2.6: Picture showing dissolution tester
21
Figure 2.7: Picture showing the paddle of dissolution tester
22
Figure 2.8: Picture showing the HPLC machine
23
2.2 Assay of Prednisolone by High Performance Liquid Chromatography
(HPLC)
Principle:
A prepared standard and sample solution are injected consequently into suitable column of High
Performance Liquid Chromatography (HPLC). The content of Prednisolone present in each
sample is calculated by comparing both the peak areas of active Prednisolone present in the
standard preparation and prepared sample.
Procedure:
Chromatographic Conditions:
Apparatus
Specifications
HPLC machine
Shimadzu HPLC-prominence integrated with
spectrophotometric UV detector
Column
4.6mmX 30cm, C18
Mobile phase, Mixture of Solution
Water
saturated
butyl
chloride,
Tetrahydrofuran, Methanol and Glacial acetic
acid (95:14:7:6).
Flow rate
1.0µl
Wavelength
254nm
Load
10µl
Temperature
40°C
24
Standard preparation:
5mg of working standard of prednisolone was weighed and transferred into a clean and dry 25ml
volumetric flask. Solution was made by adding diluting solution and was put in the sonicator for
5 minutes to make homogenous solution. 5ml of the above solution was transferred into a clean
and dry 50ml volumetric flask and diluted with diluting solution. The solution was mixed well in
the sonicator to make a homogenous solution of 20µg/ml. the solution was injected to two vials
through 0.45µ disk filter. These were called as standard solutions.
Sample preparation:
Approximately 5mg Prednisolone tablets were weighed and made fine powder by crushing with
mortar and pestle. Then the fine powdered sample was transferred into a clean and dry 25ml
volumetric flask. The 10ml of diluting solution was added and shaken well. The solution was
then put in the sonicator for 5 minutes and the volume was adjusted to the mark with the diluting
solution and mixed well. 5ml of the above solution was then transferred into a 50ml clean and
dry volumetric flask. 20ml of diluting solution was added and shaken well. The solution was put
in the sonicator for 5minutes and made up to the mark with diluting solution. The concentration
of the sample is the 20µg/ml. the solution was mixed well and injected into four vials through
0.45µ disk filter. These were called as sample solution. The above procedure was followed for
twelve different companies and their tablets.
Procedure:
Two vials containing standard solution and four vials containing sample solution were placed
into the tray of the auto sampler of Shimadzu HPLC machine. The instrument was started to run
and the chromatography was recorded.
Calculation:
The quantity of Prednisolone was calculated in sample using the following equation:
Prednisolone Content %:
Peak area of sample solution weight of standard (mg) Potency of standard
Peak Area of standard solution
Weight of sample (mg)
25
2.3 In-vitro dissolution study
Principle:
Release rate of Prednisolone tablet is carried on according to the general procedure of United
States Pharmacopoeia (USP). Samples of dissolution fluid are withdrawn and analyzed by UV
Spectrophotometer. The measurement is done at the wavelength at which the absorption is
maximum. By comparing with absorbance of standard solution, the amount of active
Prednisolone in tablets released is calculated.
Conditions:
Apparatus
USP 2 Paddle
Dissolution medium
900ml pH 7, Distilled water
Temperature
37°C (±0.5)
Stirring Speed
50rpm
Time
30 minutes
Preparation of Standard Solution:
50mg of working standard of Prednisolone was weighed and transferred into a clean and dry
100ml volumetric flask. Then 90ml of distilled water was added to the volumetric flask and
shaken. The volumetric flask is put in the sonicator for 5 minutes and made up to the mark. From
the above solution 10ml is taken in another clean and dry 100ml volumetric flask and 50ml
distilled water is added to make the solution. The solution is put in sonicator for 5minutes and
the volume is adjusted to make up the mark. Concentrations of 1mg.ml, 2mg/ml, 3mg/ml,
4mg/ml and 5mg/ml.
26
Standard curve of Prednisolone:
Concentration(mg/ml) Absorbance
0
0
1
0.07
2
0.13
3
0.19
4
0.24
5
0.326
Table 2.4: Standard curve of Prednisolone
Figure 2.3.1: Standard curve of Prednisolone
27
Preparation of sample solution:
900ml of distilled water was placed into each of six dissolution vessels and the temperature was
set to 37°C(±0.5). Weighed tablets of Prednisolone were transferred to each six baskets. The
baskets were immersed into the medium to a distance 25±2 mm between the basket and bottom
of the vessel. The apparatus was started to operate at the specified rpm. At the end of 1st hour,
10ml samples were withdrawn from each vessel and filtered through Whatman filter paper
discarding first few ml of filtrate. The withdrawn quantity of samples was replaced by fresh
dissolution medium to maintain constant volume of dissolution medium. 4ml of the filtrate were
diluted with distilled water into 10ml volumetric flask and mixed well.
Then the absorbance of the above solution in a 1cm silica cell were measured at the wavelength
of maximum absorbance at 246nm by UV-visible spectrophotometer using distilled water as
blank.
The amount of drug present in the samples was calculated with the help of straight-line equation
obtained from the calibration curve of Prednisolone. The dissolution study was continued for 1
hour to get a simulated picture of the drug release in the in-vitro condition
28
2.4 Physical parameters of Prednisolone:
Weight variation: A fundamental quality attribute for all pharmaceutical preparations is the
requirement for a constant dose of drug between individual tablets. Small variations between
individual preparations are accepted.11 The test for uniformity of weight is carried out by
collecting sample of tablets, from a batch and determining their individual weight. The average
weight of the tablets is then calculated. The sample complies with the standard if the individual
weights do not deviate from the mean more than is permitted in terms of percentage.
Thickness: The thickness of a tablet is the only dimensional variable related to the process. At a
constant compressive load, tablet thickness varies with changes in the die fill, with particle size
distribution and packing of particle mix, being compressed and with tablet weight while with a
constant die fill, thickness varies with variations in compressive load. Tablet thickness is
consistent batch to batch or within a batch only if the tablet granulation or powder blend is
adequately consistent in particle size and size distribution, if the punch tooling is of consistent
length, and if the tablet press is clean and in good working order. The thickness of individual
tablets can be measure with slide calipers which permits accurate measurements and provides
information on the variation between tablets. Tablet thickness should be with in ±5% variation
of standard value.
Hardness: Tablets require a certain amount of strength or hardness and resistance to friability, to
withstand mechanical shocks of handling in manufacture, packaging and shipping. Adequate
tablet hardness and resistance to powdering and friability are necessary requisites for consumer
and acceptance. Monitoring of tablet hardness is especially important for drug products that
possess real or potential bioavailability problems or that are sensitive to altered dissolution
release profiles as a function of the compressive force employed.
Friability: The laboratory friability tester is known as Roche friabilator. This device subjects a
number of tablets to the combined effects of abrasion and shock by utilizing aplastic chamber
that revolves at 25rmp dropping the tablets a distance of six inches with each revolution.
Normally a reweighed tablet sample is placed in the friabilator which is then operated for
29
100revolutions. The tablets are then dusted and reweighed. Conventional compressed tablets that
lose less than 0.5 to 1.0% of their weight are generally considered acceptable.
Disintegration: The first important step toward solution is breakdown of the tablet into smaller
particles or granules a process known as disintegration. The time that it takes a tablet to
disintegrate is measured in a device described in the USP. The USP device to test disintegration
uses 6 glass tubes that are 3 inches long, open at the top and held against a 10 mesh screen at the
bottom end of the basket rack assembly. To test for disintegration time, one tablet is placed in
each tube and the basket rack is positioned in a 1 liter beaker of water, at 37 ± 2°C such that the
tablets remain 2.5cm below the surface of the liquid on their upward movement and descend not
closer than 2.5cm from the bottom of the beaker. A standard motor driven device is used to move
the basket assembly containing the tablets up and down through a distance of 5 to 6 cm at a
frequency of 28 to 32 cycles per minute. Perforated plastic discs may also be used in the test.
These are placed on top of the tablets and impart an abrasive action to the tablets.
2.5 Collection of sample
The samples for this project where purchased from different retail pharmacies from the following
areas: Mohakhali wireless gate, Banani road 11, Kallynpur bus stand and Gulshan. All the
purchased samples were stored in the favorable conditions and away from direct sunlight. The
samples were taken and verified before carrying out any type of experiment on them.
30
Chapter 3:
Result and
Discussion
31
Chemical analysis:
3.1 HPLC assay values of Prednisolone tablets of different samples % Prednisolone content
Tablet
number
Sample
Sample
Sample
Sample
Sample
Sample
5
6
Sample
Sample
Sample
Sample
Sample
Sample
1
2
3
4
(multi-
(Multi-
7
8
9
10
11
12
(local)
(local)
(local)
(local)
nationa
nationa
(local)
(local)
(local)
(local)
(local)
(local)
l)
l)
1
99.66
79.98
82.83
83.28
96.03
97.81
95.65
93.36
91.85
82.37
76.89
76.22
2
97.62
77.93
81.52
80.52
97.78
97.43
97.38
99.92
91.75
82.32
76.87
75.76
3
97.98
78.3
66.52
84.02
93.75
96.34
93.38
95.73
91.8
82.23
74.64
75.96
4
96.74
77.05
60.64
83.34
93.57
95.72
93.20
95.37
91.75
82.16
73.88
75.72
5
95.9
76.21
52.49
83.71
92.43
94.98
92.06
96.55
91.72
82.09
72.75
75.59
6
95.06
75.37
44.33
84.08
91.29
94.25
90.93
97.74
91.7
82.02
71.63
75.46
Table 3.1: Percentage of Prednisolone content of tablets of different samples
32
HPLC Assay
120
% prednisolone content
100
80
Series1
60
Series2
Series3
Series4
40
Series5
Series6
20
Series7
Series8
0
Figure 3.1: Bar chart showing percentage of Prednisolone content of tablets of different
The results of HPLC analysis are presented in the bar chart above, from the above bar chart we
can see that the percentage of Prednisolone content varies from one sample to another. The
lowest percentage content of Prednisolone was found of sample 12was 75.21%. The highest
percentage content of Prednisolone was found for sample 6 and that was 97.81%. According to
USP monographs HPLC assay should be within 90%-110%, from the result above we observe
six samples give HPLC assay more than 90% the rest of the six samples are below 90% HPLC
assay.
33
Figure 3.1.1: HPLC report of Prednisolone standard 1
34
Figure3.1.2: HPLC report of Prednisolone standard 2
35
Figure3.1.3: HPLC report of Prednisolone sample 1
36
Figure3.1.4: HPLC report of Prednisolone sample 2
37
Figure 3.1.5: HPLC report of Prednisolone sample 3
38
Figure 3.1.6: HPLC report of Prednisolone sample 4
39
Figure 3.1.7: HPLC report of Prednisolone sample 5
40
Figure 3.1.8: HPLC report of Prednisolone sample 6
41
3.2 In-vitro dissolution study results
% Drug Released
Sample
Sample
Sample
Sample
5(Multi-
6 (Multi-
11
12
(local)
(local)
56.58
46.75
48.25
78.38
55.95
48.71
49.78
76.75
74.82
56.75
49.57
48.62
95.84
75.85
78.81
55.85
48.35
49.35
72.85
92.65
72.59
78.65
52.59
47.65
48.25
72.21
70.32
93.52
73.85
77.52
54.81
49.25
48.72
10.85
75.85
71.20
92.85
75.25
70.95
55.25
48.45
49.65
11.35
78.65
79.85
91.65
79.57
72.56
59.57
49.51
50.25
Sample
Sample
Sample
Sample
Sample
Sample
Sample
Sample
Sample
Number
1 (local)
2 (local)
3 (local)
4 (local)
7 (local)
8 (local)
9 (local)
10(local)
1
79.40
61.78
12.20
11.45
70.74
78.56
94.14
76.58
76.34
2
74.82
62.29
11.54
10.85
79.57
79.85
90.74
75.95
3
72.46
60.08
10.86
12.47
72.46
72.35
92.10
4
71.95
69.57
12.56
12.32
76.85
75.27
5
78.67
60.76
11.65
10.75
71.65
6
79.67
61.61
12.45
11.95
7
70.65
60.25
10.98
8
72.45
60.59
11.54
national) national)
Table 3.2: Table of in-vitro dissolution of Prednisolone tablets of different samples
42
In-vitro Dissolution
100
90
80
% Drug Released
70
60
Series1
50
Series2
Series3
40
Series4
Series5
30
Series6
Series7
20
Series8
10
0
Figure 3.2: Bar chart of in-vitro
vitro dissolution of Prednisolone tablets of different companies
According to USP not less than 75% of the labeled amount of Prednisolone should be dissolved
in 30 minutes, whereas the results show only six samples are above 75%.Tablets require
undergoing dissolution in order to be absorbed in the gastro-intestinal
intestinal tract. If tablets do not
undergo dissolution no absorption will take place. Only six brands passed the dissolution test,
samples of six brands where below 75%.
43
3.3 Physical analysis:
All physical tests parameters for the tablets are done according to USP (United States
Pharmacopeia) and BP(British Pharmacopeia). The parameters are shape, color, appearance and
size.
Sample number
Shape
Sample 1(local)
Oval
Sample 2(local)
Arc triangle
Sample 3(local)
Arc triangle
Sample 4(local)
Round
Sample 5(multi-national)
Round
Sample 6 (multi-national)
Round
Sample 7(local)
Round
Sample 8(local)
Oval
Sample 9 (local)
Oval
Sample 10( local)
Oval
Sample 11( local)
Oval
Sample 12 (local)
Oval
Table 3.3: Table showing shapes of different company tablets
44
3.4 Weight Variation:
Weight (gm)
Tablet
Sample
Sample
Sample
Sample
Sample 5
Sample 6
Sample
Sample
Sample
Sample
Sample
Sample
number
1(local)
2 (local)
3 (local)
4
(multi-
( Multi-
7 (local)
8 (local)
9 (local)
10
11
12
( local)
national)
national)
(local)
(local)
(local)
1
0.138
0.131
0.18
0.18
0.101
0.098
0.066
0.066
0.151
0.154
0.151
0.148
2
0.133
0.142
0.173
0.177
0.100
0.100
0.066
0.065
0.147
0.151
0.152
0.155
3
0.134
0.134
0.181
0.179
0.100
0.098
0.067
0.066
0.156
0.154
0.146
0.158
4
0.136
0.131
0.179
0.176
0.100
0.100
0.065
0.067
0.148
0.151
0.144
0.154
5
0.134
0.138
0.175
0.179
0.098
0.101
0.065
0.065
0.153
0.153
0.153
0.152
6
0.138
0.134
0.179
0.175
0.100
0.098
0.065
0.063
0.152
0.152
0.157
0.149
7
0.131
0.136
0.176
0.179
0.102
0.100
0.065
0.065
0.151
0.153
0.154
0.152
8
0.142
0.134
0.179
0.181
0.100
0.100
0.065
0.068
0.154
0.148
0.154
0.153
9
0.134
0.138
0.177
0.173
0.098
0.098
0.063
0.067
0.154
0.147
0.152
0.157
10
0.131
0.135
0.180
0.180
0.100
0.097
0.066
0.064
0.151
0.152
0.154
0.158
Table 3.4: Table showing weight variation of ten tablets from different samples
45
Weight Variation
0.2
0.18
0.16
0.14
Wieght (gms)
0.12
Series1
Series2
0.1
Series3
Series4
0.08
Series5
Series6
0.06
Series7
Series8
0.04
Series9
Series10
0.02
0
Figure 3.3: Bar chart showing weight variation of different samples
From the bar chart of weight variation it can be concluded that all the tablets are of uniform
weight. The average weight of all tablets of each sample is in the same range.
46
3.5 Thickness:
Thickness( cm)
Sample
Sample
Sample 5
Sample 6
Sample
Sample
Sample
Sample
Sample
Sample
3
4(
(Multi-
(Multi-
7
8
9
10
11
12
(local)
local)
national)
national)
(local)
(local)
(local)
(local)
(local)
(local)
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.31
0.31
0.33
0.31
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.31
0.32
0.32
0.33
3
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.31
0.31
0.31
0.32
4
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.32
0.32
0.33
0.31
5
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.33
0.3
0.32
0.32
6
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.31
0.3
0.3
0.33
7
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.33
0.34
0.32
0.31
8
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.32
0.32
0.33
0.32
9
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.31
0.32
0.32
0.33
10
0.3
0.3
0.35
0.35
0.2
0.2
0.2
0.2
0.33
0.31
0.33
0.3
Tablet
Sample
Sample
number
1(local)
2 (local)
1
0.3
2
Table 3.5: Table showing thickness variability of different samples
47
Thickness variability
0.4
0.35
Thickness(cm)
0.3
0.25
Series1
Series2
0.2
0.15
0.1
Series3
Series4
Series5
Series6
Series7
0.05
0
Series8
Series9
Series10
Figure3.4: Bar chart showing thickness variability of different samples
All the tablets of different companies have a uniform thickness. There is no major variability
in their thickness. There is only variation from one sample to another
48
3.6 Hardness:
Hardness(kg)
Sample
Sample 5
Sample 6
Sample
Sample
Sample
4(
(multi-
(Multi-
10
11
12
local)
national)
national)
(local)
(local)
(local)
8.25
9.21
5.62
5.65
4.65
4.73
2.75
2.78
3.65
3.27
2.24
10.47
12.56
5.18
5.43
4.81
4.15
2.98
2.54
3.74
3.45
2.63
2.84
10.55
11.65
6.06
5.34
3.8
4.69
2.56
2.89
3.42
3.86
4
2.02
3.67
12.25
10.85
5.38
4.17
3.84
4.28
2.78
2.84
3.21
3.92
5
3.72
2.48
9.10
10.31
5.86
4.72
4.73
4.95
2.68
2.57
3.52
3.84
6
2.26
2.95
8.77
9.45
5.42
4.38
4.16
4.75
2.49
2.82
3.58
3.73
7
2.67
2.98
10.11
9.87
4.81
4.24
4.77
4.64
2.65
2.92
4.57
3.41
8
2.39
2.52
10.55
10.75
4.41
5.81
3.96
3.97
2.58
2.71
3.81
3.25
9
4.21
2.54
8.21
11.85
4.85
5.63
3.15
4.27
2.48
2.82
3.72
4.85
10
2.55
3.24
9.1
12.34
5.54
4.97
4.37
4.87
2.29
2.45
3.14
3.24
Tablet
Sample
Sample
Sample
number
1(local)
2 (local) 3 (local)
1
2.68
2.92
2
3.48
3
Sample
Sample
Sample
7 (local) 8 (local) 9 (local)
Table 3.6: Table showing hardness variability of different samples
49
Hardness test
14
12
Hardness (kg)
10
8
Series1
Series2
Series3
6
Series4
Series5
Series6
Series7
4
Series8
Series9
Series10
2
0
Figure 3.5 Hardness variability of ten tablets of different samples
Hardness of each tablet of each company varies with tablets, but they are in the same range.
Only two samples show very high hardness around the range of 10-12 kg.
50
3.7 Friability:
Total weight of 10 tablets (gm)
Sample
Sample
Sample
Sample
1(local)
2 (local) 3 (local) 4 (local)
Sample 5
Sample 6
(Multi-
(Multi-
national)
national)
Sample
Sample
Sample
7 (local) 8 (local) 9 (local)
Sample
Sample
Sample
10
11
12
(local)
(local)
(local)
before
1.352
1.452
1.785
1.654
0.99
1.102
0.654
0.665
1.513
1.515
1.518
1.52
after
1.351
1.452
1.785
1.654
0.99
1.102
0.653
0.665
1.512
1.515
1.518
1.52
Table 3.7: Friability test of different samples and their total weight before and after the test
51
Friability test
2
1.8
1.6
Total weight (gms)
1.4
1.2
1
0.8
Series1
0.6
Series2
0.4
0.2
0
Figure 3.6: Bar chart of friability test of different samples and their total weight before and
after the test
Total weight of 10 tablets before and after the friability test is found the same. There was no
significant loss in weight of the tablets after the test for all the samples.
52
3.8 Disintegration time:
Disintegration time (minutes)
Tablet
Sample
Sample
Sample 3
Sample 4
number
1(local)
2 (local)
(local)
( local)
1
8
7
Did not
Did not
disintegrate
disintegrate
2
8
7
Did not
Did not
disintegrate
disintegrate
3
8
7
Did not
Did not
disintegrate
disintegrate
4
8
7
Did not
Did not
disintegrate
disintegrate
5
8
7
Did not
Did not
disintegrate
disintegrate
6
8
7
Did not
Did not
disintegrate
disintegrate
Sample 5
Sample 6
Sample
Sample
Sample
Sample
Sample
Sample
(multi-
( Multi-
7
8
9
10
11
12
national)
national)
(local)
(local)
(local)
(local)
(local)
(local)
2
2
3
3
6
6
8
8
2
2
3
3
6
6
8
8
2
2
3
3
6
6
8
8
2
2
3
3
6
6
8
8
2
2
3
3
6
6
8
8
2
2
3
3
6
6
8
8
Table 3.8: Table showing the disintegration time of different samples
53
Disintegration time
9
8
Disintegration time (minutes)
7
6
5
Series1
4
3
2
Series2
Series3
Series4
Series5
1
Series6
0
Figure 3.7: Bar chart showing the different disintegration time of different samples
Disintegration could be related to dissolution and similarly availability of drug to body
(absorption) and finally the therapeutic efficacy of product. The result showed that
disintegration time of all the selected tablets was found to be within specified limits of USP
and BP. According to USP, uncoated tablets have disintegration time standards as low as 5
minutes. For sample 3 and 4 it is seen no disintegration takes place. Which shows the drug
does not undergo dissolution and is substandard.
54
4. Conclusion
Although a wide range of synthetic glucocorticoids are now available, prednisolone still
remains the most popular choice in glucocorticoid therapy, especially for oral
administration.15
Falsified and substandard drugs may contain toxic ingredients; some of the most compelling
stories of pharmaceutical crime are of frank poisoning. By far the more common problem
however, is medicine that simply does not work. Poor quality medicines cause treatment
failure, but doctors do not generally suspect medicines as a cause of disease progression.
Lifesaving medicines can be of poor quality, which may be an uncounted root cause of high
mortality in low- and middle-income countries. No class of drug is immune to being
compromised. Medications for chronic and infectious diseases alike have been found falsified
and substandard. A considerable body of research indicates that inexpensive antimicrobial
drugs in low- and middle-income countries are frequently poor quality. This not only put
patients at risk, but encourages drug resistance, thereby threatening population health for
future generations. Falsified and substandard drugs increase costs to patients and health
systems. Medicines are expensive; patients and governments waste money on ineffective
ones. Lingering illnesses decrease productivity, causing workers to forgo pay and spend more
on treatment. Through encouraging antimicrobial resistance, illegitimate medicines reduce
the effective life of a drug. Society must bear the cost of drug development, an expense that
increases as drugs become more complex.
Close monitoring of different process in pharmaceutical industries will reduce the production
time and cost, as well as will improve the quality of the product. It was found that dissolution
was the critical parameter where problem exist among different brands. Only six brands
passed the dissolution test, tablets of six brands where below 50% as well as in HPLC assay
shows some of the companies are below90%. Two samples did not undergo disintegration at
all that shows that the tablets are substandard. However, no major problem was found in
tablet variation, thickness, friability and hardness. From the experiment we can conclude that
50% of the companies in the urban area are substandard, whereas 50% companies provide
standard drugs. It was noted that some of the local companies has very low price as compared
to the multi-national companies having the same good quality but some local companies has
nearly the same price as that of multi-national with low price.
55
The drug administration should make new policy and drug acts to stop adulteration and
control substandard drugs. Extend their regulatory mandate to cover manufacturers of
marketed pharmaceutical product particularly with regard to inspection of GMP compliance,
and impose rigorous requirements for labeling and certificates of analysis for consignments
moving in international commerce. Introduce regulations that require APIs and all other
starting materials intended for the formulation of medicinal products to be clearly labeled
“for pharmaceutical use” or with a suitable pictogram. Establish within the regulatory
authority a multidisciplinary group to investigate illicit activities promptly and professionally.
Monitor free ports and strengthen collaboration with law enforcement agencies including
customs officials, and offices of criminal investigation, at national and international level.
Seek to enact legislation that permits sequestration of assets gained by unlawful activity and
seizure and destruction of products involved.
In conclusion it can be said that the different brands of well reputed local pharmaceutical
companies can be compared with that of multi-national companies. As in Bangladesh not
only in rural areas but also in urban areas more medicine is required of high standard as more
patients require better healthcare. However, products of some less known local
pharmaceutical industry needs improvements in quality and should be strictly monitored for
manufacturing of substandard dosage forms.
56
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systemically administered glucocorticoids. ClinPharmacokinet. 2005;44(1):61-98. Review.
4. BuraimohA.A.,et al; The Srudy of the effects of prednisolone on the cerebral cortex of
Wistar Rats, Int.J.Pharm.Drug Anal. Vol: 2 Issue:3 Page:329-333
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The
world
health
report
2000-Health
systems:
improving
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Prednisone or Prednisolone for the treatment of chronic active hepatitis? A comparison of
plasma availability, Br.J.clin.Pharmac. (1978),5, 501-505
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December 2012.(http://www.drugs.com/uk/prednisolone-tablets-1mg-leaflet.html)
10. MHRA PAR Prednisolone 5mg Tablets BP, PL06453/0055
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Eosinophils and nitric oxide metabolites in the sputum of patients with exacerbated asthma,
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lymphoblastoid cells, Waddell A.W., Curie A.R., Biochem, J. (1977) 168,323-324
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English, J Chakraborty, V Marks, D J Trigger, and A G Thomson, Br. J. clin. Pharmac.
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57